Efficacy and Safety of Subcutaneous Dermatophagoides Allergoid Immunotherapy in Allergic Rhinitis/Rhinoconjunctivitis with or without Asthma
- Trial ID
- 2024-514090-21-00
- Protocol
- MM09-SIT-023
- Sponsor
- Inmunotek S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **clinical efficacy** of subcutaneously administered polymerised allergen extracts compared to placebo in subjects with moderate-severe intermittent or persistent **rhinitis/rhinoconjunctivitis** according to the ARIA classification, with or without mild-moderate controlled intermittent or persistent **asthma** as defined by GEMA 5.0. This is clinically relevant as it aims to provide an effective treatment option for patients suffering from these allergic conditions, potentially improving their quality of life and reducing the burden of symptoms.
Secondary objectives include assessing the safety and efficacy of the polymerised extracts under the specified conditions by comparing the active and placebo groups at both the beginning and the end of the study across all secondary variables. This will help to ensure that the treatment is not only effective but also safe for long-term use in the target population.
Participants
The clinical trial involves a study population comprising both **male** and **female** subjects aged between 12 and 65 years. The participants are individuals diagnosed with moderate-severe intermittent or persistent **allergic rhinitis/rhinoconjunctivitis** with or without controlled mild-moderate intermittent or persistent allergic asthma. The trial population was selected based on specific criteria, including a confirmed clinical history of inhalant allergy to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae, and the ability to comply with the dosing regimen. Participants are required to have a smartphone for recording symptoms and medication use. The study includes individuals who have signed informed consent and are able to adhere to the trial's requirements. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified, but participants must be able to comply with the trial's demands. The trial includes a vulnerable population, and women of childbearing potential must use adequate contraception during the study. The sponsor has not disclosed the total number of participants involved in the trial.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, placebo-controlled study designed to evaluate the efficacy and safety of subcutaneous immunotherapy in patients with moderate-severe intermittent or persistent **allergic rhinitis/rhinoconjunctivitis** with or without controlled mild-moderate intermittent or persistent **allergic asthma**. The trial involves the administration of polymerised allergen extracts, specifically targeting individuals sensitized to **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**. The study is expected to run until December 31, 2025, with participant recruitment having commenced on October 6, 2020.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical history, and specific **IgE** levels. Following successful screening, participants will be randomized to receive either the investigational product, Clustoid MM09, or a placebo, both administered as a **suspension for injection** via subcutaneous use. The maximum daily dose is 0.5 ml, with a total treatment period of up to 12 months. Study visits will include regular follow-up assessments to monitor efficacy and safety, with endpoints focusing on symptom and medication scores, quality of life, and immunological parameters. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes and any adverse events experienced during the trial.
Participant involvement is expected to last for the duration of the treatment period, approximately 12 months, unless early termination is warranted. Conditions for early termination include non-compliance with the dosing regimen, withdrawal of consent, or the occurrence of significant adverse events. The trial aims to provide comprehensive data on the clinical efficacy of the allergen extracts, contributing to the understanding and management of allergic rhinitis/rhinoconjunctivitis and asthma in sensitized individuals.
Treatment
The clinical trial involves the administration of **Clustoid MM09**, a **suspension for injection** designed for **subcutaneous use**. This experimental medication contains the active substances **Dermatophagoides farinae allergoid, glutaraldehyde-modified** and **Dermatophagoides pteronyssinus allergoid, glutaraldehyde-modified**. These substances are structurally diverse allergens, modified with glutaraldehyde, and are intended for use in patients with rhinitis/rhinoconjunctivitis, with or without mild to moderate asthma. The maximum daily dose of Clustoid MM09 is 0.5 ml, with a total treatment period not exceeding 12 months. The administration schedule is designed to ensure participant compliance, with regular monitoring throughout the trial.
The trial also includes a **placebo** group to serve as a comparator for evaluating the efficacy and safety of Clustoid MM09. The placebo is formulated to match the experimental medication in appearance and administration method, ensuring the double-blind nature of the study. Participants receiving the placebo will follow the same dosing schedule and monitoring protocols as those receiving Clustoid MM09. This design allows for a robust comparison of outcomes between the experimental and control groups, contributing to the overall assessment of the treatment's clinical efficacy.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of moderate-severe intermittent or persistent rhinitis/rhinoconjunctivitis, with or without controlled mild to moderate intermittent or persistent asthma, in subjects sensitized to **Dermatophagoides pteronyssinus** and/or **Dermatophagoides farinae**. The primary endpoint involves assessing the combined symptom score and medication intake from baseline to the end of the trial. Secondary endpoints include a variety of symptom and medication scores such as the Rhinitis/Rhinoconjunctivitis Symptom Score (RSS), Rhinitis/Rhinoconjunctivitis Medication Score (RMS), Asthma Combined Symptom and Medication Score (ACSMS), Asthma Symptom Score (ASS), and Asthma Medication Score (AMS). Additional secondary endpoints include the Asthma and Rhinitis/Rhinoconjunctivitis Symptom Score (ARSS), Asthma and Rhinitis/Rhinoconjunctivitis Medication Score (ARMS), and the Combined Symptom and Medication Score for Asthma and Rhinitis/Rhinoconjunctivitis (ARCSMS).
Further assessments will be made on symptom-free days and medication-free days for both rhinitis/rhinoconjunctivitis and asthma, as well as the time since the first onset of asthma exacerbation, including the number, severity, and duration of these exacerbations. Quality of life will be evaluated using the ESPRINT-15 questionnaire for rhinitis and the asthma symptom control questionnaire (GINA) for asthma. The Visual Analogue Scale (VAS) will also be utilized. Serum immunological parameters, including total IgE, specific IgE, and specific IgG4, will be measured to provide additional insights into the immunological response. The consumption of health resources and the safety of specific immunotherapy will be monitored, focusing on the overall rate, severity, and ratio of any adverse events per administration and per subject, as well as the assessment of administration site reactions, systemic reactions, and any concomitant medication administered for the treatment of adverse events.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects who have signed the informed consent form.
- Subjects of both sexes aged between 12 and 65 years old.
- Subjects with a confirmed clinical history of inhalant allergy (intermittent or persistent moderate-severe rhinitis and/or rhinoconjunctivitis according to the ARIA classification with or without controlled intermittent or persistent mild-moderate asthma according to the GEMA 5.0 definition) caused by allergy to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae.
- Subjects who have had a prick test result ≥ 5 mm in diameter greater for Dermatophagoides pteronyssinus and/or for Dermatophagoides farinae. Positive and negative control test results must be consistent.
- Subjects with a specific IgE value > 3.5 KU/L (ImmunoCAP® or Immulite) for complete extract of Dermatophagoides pteronyssinus and/or for Dermatophagoides farinae or for some of the molecular components of these allergenic sources
- Subjects shall preferably be monosensitised to the study allergens. In the case of subjects sensitised to other aeroallergens, only those with the following characteristics (results valid 12 months prior to signing the informed consent) may be included in the study: (a) Subjects with positive skin test to Blomia tropicalis and Lepidoglyphus destructor, whose maximum specific IgE values are 3.5 KU/L. b) Subjects with negative skin test. Subjects with positive skin tests for epithelia may be included in the study, provided that they have occasional exposure and symptomatology. c) Subjects with positive skin tests for pollens, whose specific IgE values do not exceed or equal the values for the study allergens and who, in addition, do not present exacerbations in the pollen season. The maximum value of specific IgE for these allergens is 17.5 KU/L.
- Subjects with negative skin test for fungus.
- Women of childbearing age (since menarche) should submit a negative urine pregnancy test at the time of entry into the trial, prior to administration of the first dose of investigational medicinal product.
- Women of childbearing potential participating in the trial should agree to use an adequate method of contraception, defined as any act, device, or medication to prevent conception or a viable pregnancy, during the trial if sexually active.
- Subjects diagnosed with asthma according to GEMA 5.0.
- Subjects able to comply with the dosing regimen.
- Subjects owning a smartphone to record symtom and medication.
Exclusion Criteria
- Subjects who have received previous immunotherapy in the previous 5 years to epithelia, fungi and mites.
- Subjects in whom immunotherapy may be subject to absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and the European Allergy and Clinical Immunology Immunotherapy Subcommittee.
- Subjects with severe or uncontrolled persistent asthma, with an FEV1 < 70% of baseline despite adequate pharmacological treatment at the time of inclusion in the trial.
- Subjects who have previously exhibited a severe secondary reaction during diagnostic skin prick tests.
- Subjects on ß-blocker treatment.
- Subjects who are clinically unstable at the time of inclusion in the trial (acute asthmatic exacerbation, respiratory infection, febrile process, acute urticaria, etc).
- Subjects with active chronic urticaria, severe dermographism, severe atopic dermatitis, sunburn, active psoriasis with lesions in areas where skin testing will be performed, or a history of hereditary angioedema.
- Subjects with any pathology in which the administration of adrenaline is contraindicated (hyperthyroidism, hypertension, heart disease, etc.).
- Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but potentially serious and which may interfere with treatment and follow-up (epilepsy, psychomotor alteration, uncontrolled diabetes, malformations, multioperative, nephropathy, etc.).
- Subjects with autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or diagnosed with immunodeficiencies.
- Subjects whose condition prevents them from cooperating or who present severe psychiatric disorders.
- Subjects with known allergy to components of the investigational medicinal product other than the allergen.
- Subjects with lower respiratory tract diseases other than asthma such as emphysema or bronchiectasis.
- Subjects who are immediate family relatives of researchers.
- Pregnant or breastfeeding women.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 06 Oct 2020 | 150 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Clustoid MM09 | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS USE | 0.5 | 12 | PRD11315623 |
The same as active product | Placebo | N/A | — | — | — | N/A |
Clustoid MM09 | Test | SUSPENSION FOR INJECTION | SUBCUTANEOUS USE | 0.5 | 12 | PRD11315715 |